rs74138760
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_032776.3(JMJD1C):c.699C>T(p.Val233=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000987 in 1,588,958 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0044 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00063 ( 5 hom. )
Consequence
JMJD1C
NM_032776.3 synonymous
NM_032776.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.06
Genes affected
JMJD1C (HGNC:12313): (jumonji domain containing 1C) The protein encoded by this gene interacts with thyroid hormone receptors and contains a jumonji domain. It is a candidate histone demethylase and is thought to be a coactivator for key transcription factors. It plays a role in the DNA-damage response pathway by demethylating the mediator of DNA damage checkpoint 1 (MDC1) protein, and is required for the survival of acute myeloid leukemia. Mutations in this gene are associated with Rett syndrome and intellectual disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.32).
BP6
?
Variant 10-63215676-G-A is Benign according to our data. Variant chr10-63215676-G-A is described in ClinVar as [Benign]. Clinvar id is 460276.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=3.06 with no splicing effect.
BS2
?
High AC in GnomAd4 at 669 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
JMJD1C | NM_032776.3 | c.699C>T | p.Val233= | synonymous_variant | 6/26 | ENST00000399262.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
JMJD1C | ENST00000399262.7 | c.699C>T | p.Val233= | synonymous_variant | 6/26 | 5 | NM_032776.3 |
Frequencies
GnomAD3 genomes ? AF: 0.00440 AC: 669AN: 152114Hom.: 3 Cov.: 32
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GnomAD3 exomes AF: 0.00116 AC: 280AN: 241810Hom.: 2 AF XY: 0.000892 AC XY: 117AN XY: 131160
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GnomAD4 exome AF: 0.000626 AC: 900AN: 1436726Hom.: 5 Cov.: 32 AF XY: 0.000583 AC XY: 414AN XY: 710028
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GnomAD4 genome ? AF: 0.00439 AC: 669AN: 152232Hom.: 3 Cov.: 32 AF XY: 0.00450 AC XY: 335AN XY: 74426
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
JMJD1C-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 11, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Early myoclonic encephalopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at